Calcium-handling abnormalities underlying atrial arrhythmogenesis in a Fontan operation canine model
Calcium-handling abnormalities underlying atrial arrhythmogenesis in a Fontan operation canine model
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Fontan 手术犬模型中房性心律失常发生的钙处理异常
DOI：
10.1007/s12519-018-0177-z
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发表时间：
2018-08
影响因子：
8.7
通讯作者：
Qian Yi Jiao
中科院分区：
文献类型：
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作者：
Zhou Wan Ping;Li Fen;Wu Jin Jin;Lu Ya Nan;Qian Yi Jiao
背景：房源性心动过速（AT）是Fontan手术患者的常见并发症。在这项研究中，我们研究了异常Ca2+处理是否有助于Fontan手术相关的心房心律失常底物。方法将杂种狗随机分为sham组和Fontan组。Fontan手术模型是通过心房肺吻合术建立的。14天后，进行电生理研究以评估AT的易损性。通过加载心房心肌细胞（CMs） fura-2 AM来测量Ca2+处理特性。全细胞膜片钳技术记录了cm的el型Ca2+(ICa−L)和Na+ -Ca2 +交换器（INCX）电流。Western blotting检测关键Ca2+处理蛋白的表达。结果方丹组AT诱导率高于假手术组（85.71比14.29%，P< 0.05）。Fontan手术导致Ca2+瞬态（CaT）振幅和肌浆网（SR） Ca2+含量降低，但增加了舒张期细胞内Ca2+浓度和心房CMs中SR Ca2+泄漏。原心房cm的自发CaT事件、诱发异位活性和incx密度增加，而tica−l密度降低（p < 0.05）。此外，Fontan操作导致SR Ca2+ATPase表达和Cav1.2表达降低，但NCX1和ser2814磷酸化的ryanodine受体2升高。钙调素依赖性蛋白激酶II的表达和功能明显增强。结论Fontan手术引起心房CM Ca2+处理异常，引起心律失常触发活动，增加了实验性Fontan犬对AT的易感性。
BackgroundAtrial tachyarrhythmia (AT) is a common complication in patients who have undergone a Fontan operation. In this study, we investigated whether abnormal Ca2+handling contributes to the Fontan operation-related atrial arrhythmogenic substrate.MethodsMongrel dogs were randomly assigned to sham and Fontan groups. The Fontan operation model was developed by performing an atriopulmonary anastomosis. After 14 days, an electrophysiological study was performed to evaluate the AT vulnerability. Ca2+handling properties were measured by loading atrial cardiomyocytes (CMs) with fura-2 AM. TheL-type Ca2+(ICa−L) and Na+–Ca2+exchanger (INCX) currents of the CMs were recorded by the whole-cell patch-clamp technique. The key Ca2+handling proteins expression was assessed by Western blotting.ResultsThe AT inducibility was higher in the Fontan group than in the sham group (85.71 vs. 14.29%,P< 0.05). The Fontan operation resulted in decreased Ca2+transient (CaT) amplitude and sarcoplasmic reticulum (SR) Ca2+content, but in enhanced diastolic intracellular Ca2+concentration and SR Ca2+leak in the atrial CMs. The spontaneous CaT events, triggered ectopic activity andINCXdensity were increased, butICa−Ldensity was reduced in CMs from the Fontan atria (allP< 0.05). Additionally, the Fontan operation resulted in decreased SR Ca2+ATPase expression and Cav1.2 expression, but in increased NCX1 and Ser2814-phosphorylated ryanodine receptor 2. The calmodulin-dependent protein kinase II expression and function were markedly enhanced in the Fontan atria.ConclusionThe Fontan operation caused atrial CM Ca2+handling abnormalities that produced arrhythmogenic-triggered activity and increased vulnerability to AT in experimental Fontan dogs.
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影响因子：
7.5
作者：
Clift, Paul;Celermajer, David
通讯作者：
Celermajer, David
影响因子：
2.8
作者：
Wolf, Cordula M.;Seslar, Stephen P.;den Boer, Karen;Juraszek, Amy L.;McGowan, Francis X.;Cowan, Douglas B.;Del Nido, Pedro;Triedman, John K.;Berul, Charles I.;Walsh, Edward P.
通讯作者：
Walsh, Edward P.
影响因子：
2.7
作者：
S. Yap;L. Harris;E. Downar;K. Nanthakumar;C. Silversides;V. Chauhan
通讯作者：
S. Yap;L. Harris;E. Downar;K. Nanthakumar;C. Silversides;V. Chauhan
影响因子：
2.7
作者：
Meng, D;Feng, L;Zhang, JN
通讯作者：
Zhang, JN
DOI：
10.1016/j.echo.2014.01.027
发表时间：
2014-04
期刊：
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
影响因子：
--
作者：
Shu-juan Li;S. Wong;Y. Cheung
通讯作者：
Shu-juan Li;S. Wong;Y. Cheung